Scaffold materials, porous or dense, are used in cell culture and tissue engineering as platforms to enhance cell attachment, proliferation and activity, leading to shorter healing time of injured or missing tissue. These scaffolding materials include, but are not limited to, some metals, certain metallic alloys, different glasses, various ceramics and polymers. In fact many natural and synthetic polymers can be used to fabricate scaffolds for implants. Amongst the most common synthetic polymers are polyesters, such as poly(D,L-lactic acid) (PDLLA), poly(lactic-co-glycolic acid) (PLGA), and thermoplastics, such as polyether ether ketone (PEEK). Polyesters degrade by forming lactic acid and glycolic acid, which are non-toxic, and they are approved by the USA Food and Drug Administration for human clinical use. Accordingly, scaffolds, implants, etc. made with polyesters are commonly used in bone tissue engineering due to their biodegradability, biocompatibility and adequate mechanical properties. In contrast scaffolding employing metals, alloys, ceramics and glasses are typically not biodegradable.
Irrespective of material, the scaffolding surface is the first region that cells contact once the scaffolding material has been implanted and generally determines their reaction to the implant. Despite being biocompatible, most synthetic polymers including polyesters and PEEK are hydrophobic, which is a parameter known to promote non-specific protein adsorption and to prevent maximum adhesion and spreading of cells. Moreover, neither polyesters nor PEEK have any surface group that can specifically enhance cell adhesion, growth or function. As a result surface modification of these materials is crucial to enhance the implant's integration in the body. When the implants are used in orthopedic applications, surface modification can help the formation of hydroxyapatite (Ca10(PO4)6(OH)2) (commonly abbreviated to HA), which is the mineral component of bones through a process known as biomineralization.
In a similar manner, PEEK is a material used within bone implants for its excellent mechanical properties, biocompatibility and radiolucency. However, in common with the user of polyesters for scaffolds, a key limitation is low cell adhesion and bone integration due to the hydrophobic properties of its surface. Accordingly, it would be beneficial to similarly modify the surface of the PEEK implants. Different modification techniques such as such as plasma spray coating, photochemical deposition, radio-frequency magnetron sputtering coating and electron beam deposition have been used in the prior art to add particles, coatings and functional groups to the surface of PEEK. However, major drawbacks include insufficient cohesion, delamination, and high costs of production.
Further, in many instances these processes require line of sight access to the surface being modified which limits their use on complex geometries, porous structures, etc. Accordingly, as with polyesters the surface modification of PEEK would benefit from the availability of a processing methodology to overcome the limitations within the prior art.
Plasma treatment has been successfully applied to modify two-dimensional polymeric surfaces (e.g. films) but in three-dimensional (3D) implants, especially if porous, the technique is less effective as the plasma reacts quickly with the outer surfaces, whilst the inner pores do not get modified. In contrast physical adsorption or chemical hydrolysis (for polyesters) allow implants to be modified both on the outside and inside surfaces. With physical adsorption implants are immersed in a solution containing biomolecules such as natural adhesive proteins and whilst the technique has the advantage of simplicity, it leads to the formation of weak bonds and the biomolecules can detach under physiological conditions. Polyester hydrolysis generates carboxylates and hydroxyl groups which can then bind biomolecules. However, the polymeric backbone of the implant is degraded during this treatment.
Diazonium chemistry is a wet chemistry technique able to modify a variety of surfaces, including polymers, and a “grafting” process can be performed by applying an external potential or exploiting redox reactions occurring between a diazonium salt or its aniline precursor, which is transformed into a reactive radical, and the material to be modified. Accordingly, it would be beneficial to apply this method which has been successful at introducing a number of functional groups, including alkyls, halides, carboxyls, nitro groups, perfluorinated chains, redox species, and dendrimers in other environments to the surface modification of biomedical scaffolds. It would be further beneficial to exploit diazonium chemistry such that the aniline layer formed can be easily reactivated, forming a so-called “self-adhesive surface”, and made react with any nucleophilic compound, thus allowing introduction of a wide range of functional groups to the desired surface.
Other aspects and features of the present invention will become apparent to those ordinarily skilled in the art upon review of the following description of specific embodiments of the invention in conjunction with the accompanying figures.